Phase Ib/II Trials of RAD001 in Triple Negative Metastatic Breast Cancer

NCT01939418 | Terminated Phase 1

• 2 other identifiers: NCCCTS-13-67012491
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This study consists of two parts. In a phase Ib part, investigators will explore the recommended dose of gemcitabine, cisplatin, and RAD001 combination in patients with metastatic TNBC. After completing the phase Ib part, investigators will review the data and discuss with Novartis before the start of a phase II part. In the phase II part, investigators will compare the efficacy of the gemcitabine and cisplatin with or without RAD001 in patients with metastatic TNBC.

Conditions

Metastatic Breast Cancer

Keywords

metastatic breast cancer; triple negative breast cancer; gemcitabine; RAD001

Outcome Measures

Primary Outcomes (2)

• The recommended dose of the combination of gemcitabine, cisplatin and RAD001 (everolimus) in patients with metastatic triple-negative breast cancer

  phase IB part

  up to 1 year

• Efficacy of gemcitabine and cisplatin with or without RAD001 in patients with metastatic triple-negative breast cancer by evaluating progression free survival (PFS)

  phase II part

  up to 5 years

Secondary Outcomes (5)

• The maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gemcitabine/cisplatin/RAD001

  up to 1 year

• number of patients with adverse events as a measure of safety and tolerability

  up to 5 years

• objective response rate

  up to 1 year

• Overall survival (OS)

  up to 5 years

• check biomarkers associated with the response of RAD001: angiogenesis, metabolism, immune cells profiles

  up to 5 years

Study Arms (1)

RAD001

EXPERIMENTAL

gemcitabine 800mg/m2, D1 and D8 iv. every 3 weeks. cisplatin 30mg/m2, D1 and D8 iv. every 3 weeks. RAD001 5mg QD. po.

Drug: RAD001; Drug: Gemcitabine; Drug: Cisplatin

Interventions

RAD001 DRUG

Afinitor 5mg qd. po.

Also known as: Afinitor, everolimus

RAD001

Gemcitabine DRUG

gemcitabine 800mg/m2 iv. D1 and D8 every 3 weeks

RAD001

Cisplatin DRUG

cisplatin 30mg/m2 iv. D1 and D8 every 3 weeks

RAD001

Eligibility Criteria

• Age: 20 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females with histologically confirmed, metastatic or stage IV breast cancer
• ER/PgR negative or poor (Allred score ≤ 3/8) and HER2 negative breast cancer
• ECOG performance status 0-2
• Age ≥ 20 years
• Previously treated by anthracycline and taxane in adjuvant/neoadjuvant or metastatic setting
• ≤ 2 chemotherapy regimens for metastatic disease
• Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrolment.
• CNS metastasis is permitted if asymptomatic and not requiring treatment with steroids and is documented to be non-progressing at study entry
• Presence of measurable or evaluable disease by RECIST 1.1 criteria
• Adequate hematopoietic function: Absolute granulocyte count ≥1,500/mm3, platelet ≥100,000/mm3, hemoglobin ≥ 10g/mm3
• Adequate hepatic function: total bilirubin ≤ 1.5 x upper normal limit (UNL), AST/ALT ≤2.5 x UNL or ≤5 x UNL if presented with hepatic metastasis
• Fasting serum cholesterol ≤ 300mg/dl and fasting triglycerides ≤ 2.5 x UNL
• Adequate renal function: Serum creatinine ≤1.5mg/dL
• Patients should sign a written informed consent before study entry
• Patients with positive HBV-DNA of HBsAg at screening must initiate prophylaxis with appropriate antiviral medication at least one week prior to treatment start

You may not qualify if:

• Known active CNS metastasis
• Patients who received prior therapy with gemcitabine
• Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites).
• Patients with more than 3 prior chemotherapy lines for treating metastatic breast cancer.
• Patients who received prior therapy with mTOR inhibitor or PI3K inhibitor
• Known hypersensitivity to mTOR inhibitors, e.g. Sirolimus (rapamycin).
• Radiotherapy within four weeks prior to enrolment, except radiotherapy to the bone for analgesic purpose or for lytic lesions at risk of fracture. Patients must have recovered from radiotherapy toxicities prior to enrolment.
• Patients who have history of cancer other than in situ uterine cervix cancer or nonmelanotic skin cancer
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
• Active ulceration of upper gastrointestinal tract
• Other concurrent severe and/or uncontrolled conditions (e.g. uncontrolled diabetes mellitus, active untreated or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease including dyspnea at rest from any cause) that could cause unacceptable safety risks or compromise compliance with the protocol.
• Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline is not required.
• Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 saturation at rest on room air should be considered to exclude restrictive pulmonary disease, pneumonitis or pulmonary infiltrates.
• Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A at enrolment (rifabutin, rifampicin, clarithromycin, ketoconazole, itraconazole, voriconazole, ritonavir, telithromycin) continuously for at least 7 days during any time period in the last 2 weeks prior to enrolment
• Known hypersensitivity to protocol treatment

Sponsors & Collaborators

• National Cancer Center, Korea: lead

Study Sites (1)

National cancer center

Goyang-si, Gyeonggido, 410-769, South Korea

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Everolimus; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• In Hae Park, Doctor

  National Cancer Center, Korea

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 28, 2013
• First Posted: September 11, 2013
• Study Start: August 1, 2013
• Primary Completion: July 30, 2016
• Study Completion: July 30, 2017
• Last Updated: October 3, 2017

Record last verified: 2017-10

Locations

KR (1)